AUTHOR INFORMATION

Section 1 of 12

Authored by James Stephen, MD, Assistant Professor, Director of Medical Informatics, Associate Director, Kiwanis Pediatric Trauma Service, Department of Emergency Medicine, Tufts Medical School and New England Medical Center

James Stephen, MD, is a member of the following medical societies: American Academy of Emergency Medicine

Edited by Dana A Stearns, MD, Assistant Director of Undergraduate Education, Department of Emergency Medicine, Massachusetts General Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Paul Blackburn, DO, Program Director, Department of Emergency Medicine, Maricopa Medical Center; Assistant Professor, Department of Surgery, University of Arizona; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Barry Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, and Professor of Anatomy and Neurobiology, Research Director, Department of Emergency Medicine, University of Arkansas for Medical Sciences

Author's Email:	James Stephen, MD
Editor's Email:	Dana A Stearns, MD

eMedicine Journal, February 13 2007, VOLUME 8, Number 2

INTRODUCTION

Section 2 of 12

Background: Bacterial pneumonia is caused by a pathogenic infection of the lungs and may present as a primary disease process or as the final coup de grace in the individual who is already debilitated. Pneumonia may be further categorized into community-acquired pneumonia (CAP), or hospital- or institutional-acquired pneumonia (HAP or IAP, respectively).

William Henry Harrison, the ninth president of the United States, contracted pneumonia during his inauguration in 1841 and died after being in office for only 31 days. Ronald Reagan, 40th US president, died of pneumonia after years of debilitation from Alzheimer disease. Other notable persons to succumb to pneumonia include Sir Francis Bacon (1626), who died after stuffing chickens with snow while conducting freezing experiments, and Thomas Stonewall Jackson (1863), whose arm required amputation after he was shot by one of his own sentries.

Pathophysiology: Bacteria from the upper airways or, less commonly, from hematogenous spread, find their way to the lung parenchyma. Once there, a combination of factors (including virulence of the infecting organism, status of the local defenses, and overall health of the patient) may lead to bacterial pneumonia. The patient may be made more susceptible to infection because of an overall impairment of the immune response (eg, HIV infection, chronic disease, advanced age) and/or dysfunction of defense mechanisms (eg, smoking, chronic obstructive pulmonary disease [COPD], tumors, inhaled toxins, aspiration). Poor dentition or chronic periodontitis is another predisposing factor.

Frequency:

• In the US: More than 3 million cases occur annually in the United States. Pneumonia is more prevalent during the winter months and in colder climates. This condition is most likely from viral upper and lower respiratory infections, which increase in winter and result in impaired host defenses to bacterial superinfection.

Mortality/Morbidity: Left untreated, pneumonia may have an overall mortality rate of more than 30%. The individual's risk of mortality is dependent on the particular infectious agent and host response. Even with appropriate treatment, the risk of mortality may be high if the host is ill or infirm.

The Pneumonia Severity Index (PSI) may be used as a guide to determine a patient's mortality risk, but it tends to overestimate the actual risk in many cases.

Particularly virulent organisms, such as Klebsiella and Legionella species, may confer a higher mortality rate.

• Morbidity may include destruction of lung tissue from infection, with subsequent scarring. Affected areas may be incapable of gas exchange, reducing respiratory reserve.

• In a patient with preexisting respiratory disease, onset of bacterial pneumonia may result in a downward spiral of infections, further impairment of respiratory status, and repeated infections owing to reduced local and systemic immune responses.

• Bronchiectasis may be a sequela of bacterial pneumonia. Infections with Staphylococcus and Klebsiella organisms result in subsequent bronchiectasis, especially if treatment is delayed.

• Destroyed alveoli and small-to-medium airways may be replaced by dilated blind saccules filled with purulent material. Ongoing, chronic inflammation usually occurs in the surrounding area and may destroy local adjacent lung tissue over time.

• Empyema and lung abscess may occur as direct complications of bacterial pneumonia.

• Pneumonia has been associated with increased incidence of placental abruption in pregnant patients.

Sex: Incidence is greater in males than in females.

Age: In general, advanced age increases the risk of contracting the disease and mortality. In patients who are elderly, comorbidity and a diminished immune response and defense against aspiration increase the risk of bacterial pneumonia. In a 20-year US study, the average overall mortality rate in pneumococcal pneumonia with bacteremia was 20.3%; patients older than 80 years had the highest mortality rate, which was 37.7%.

CLINICAL

Section 3 of 12

History: The clinical presentation varies from the mildly to extremely ill patients.

• Although not diagnostic of a particular causative agent, the characteristics of the sputum produced may suggest the presence of one bacterium instead of another.

• Pneumococci may produce bloody or rust-colored sputum.

• Pseudomonas, Haemophilus, and pneumococcal species may produce green sputum.

• Anaerobic infections may produce foul-smelling sputum.

• Klebsiella and type 3 pneumococci may produce sputum resembling currant jelly.

• Rigors or severe shaking chills may be observed in any infectious process. For unclear reasons, the presence of rigors may suggest pneumococcal pneumonia more often than pneumonia caused by other bacterial pathogens.

• The patient also may have headache, malaise, nausea, vomiting, and diarrhea. Although these symptoms may be observed in any systemic illness, their presence with bacterial pneumonia is suggestive of infection with Legionella species.

• Other findings include the following:
  • Malaise

• Myalgias

• Exertional dyspnea (dyspnea at rest with progressive disease)

• Pleuritic chest pain

• Abdominal pain

• Anorexia and weight loss

• Sudden onset of symptoms and rapid illness progression are associated with bacterial pneumonias.

Physical:

• Findings at physical examination may include the following:

• Fever

• Tachypnea

• Tachycardia or bradycardia

• Cyanosis

• Decreased breath sounds

• Wheezes, rhonchi, and rales

• Egophony on auscultation

• Pleural friction rub

• Dullness to percussion

• Altered mental status

Causes: Causes for the development of pneumonia are extrinsic or intrinsic, and various bacterial causes exist.

• Extrinsic factors include exposure to a causative agent, exposure to pulmonary irritants, or direct pulmonary injury.

• Most authors categorize bacterial pneumonias by their infectious agents, which include pneumococcal agents; Haemophilus influenzae; Klebsiella, Staphylococcus, and Legionella species; gram-negative organisms; and aspirated materials.

• Inhalation of infectious aerosols probably is the most common mode of infection. Some agents, notably Staphylococcus species, may be spread hematogenously.

• Intrinsic factors are related to the host.

• Loss of protective upper airway reflexes allows aspiration of contents from the upper airways into the lung. Various causes for this loss include altered mental status due to intoxication and other metabolic states and neurologic causes, such as stroke and endotracheal intubation.

• Local lung pathologies (eg, tumors, COPD, bronchiectasis) are predisposing factors. Smoking also impairs resistance to infection. Chronic gingivitis and periodontitis also are associated with increased risk of pneumonia.

• Bacterial pneumonia caused by Streptococcus pneumoniae remains the most common cause of all bacterial pneumonias.

• Pneumonia from H influenzae most commonly arises in the winter and early spring.

• This pneumonia more often is associated with hosts who are debilitated.

• Asthma, COPD, smoking, and a compromised immune system are risk factors for H influenzae infection.

• Klebsiella pneumonia results in an aggressive necrotizing lobar pneumonia. Patients with chronic alcoholism, diabetes, or COPD are at increased risk.

• Staphylococcus aureus pneumonia is observed in intravenous drug abusers and other individuals with debilitations. In patients who abuse intravenous drugs, the infection probably is spread hematogenously to the lungs from contaminated injection sites.

• Legionella pneumophila infections tend to occur sporadically and in local epidemic clusters. Legionella pneumonia was named after an outbreak in 1976 that affected more than 180 members of the American Legion who were staying at the same hotel for an annual convention. Twenty-nine legionnaires died, and the organism was not identified until 1977. These infections usually arise in the summer and fall and may be found in the water condensed from air conditioning systems. L pneumophila seems to have the following 2 forms:

• Pontiac fever has a viruslike presentation, with malaise, fever and/or chills, myalgias, and headache. This form of Legionella pneumonia usually subsides without sequelae.

• Frank Legionella pneumonia, the second form of the disease, is very aggressive, with a mortality rate as high as 75% unless treatment begins rapidly. It occurs in individuals who are elderly and debilitated, as well as in smokers and those with COPD, alcoholism, immunocompromise, or trauma.

• Unlike other pneumonias, Legionella pneumonia has GI symptoms associated with its infection more than 50% of the time. GI manifestations may include anorexia, nausea, vomiting, and diarrhea.

• Gram-negative pneumonias are observed in individuals who are debilitated, immunocompromised, or recently hospitalized.

• Causative organisms include Escherichia coli and Pseudomonas, Enterobacter, and Serratia species.

• Individuals living in long-term care facilities where other residents are intubated also are at risk for these infections.

• Any individual with an altered sensorium (eg, seizures, alcohol or drug intoxication) or CNS impairment (eg, stroke) may have a reduced gag reflex, which allows aspiration of stomach or oropharyngeal contents and which enables aspiration pneumonias.

• Causative organisms may include Moraxella catarrhalis and Bacteroides, Peptostreptococcus, and Fusobacterium species.

DIFFERENTIALS

Section 4 of 12

Asthma
Bronchitis
Chronic Obstructive Pulmonary Disease and Emphysema
Epiglottitis, Adult
Foreign Bodies, Trachea
Pediatrics, Bacteremia and Sepsis
Pediatrics, Bronchiolitis
Pediatrics, Croup or Laryngotracheobronchitis
Pediatrics, Epiglottitis
Pediatrics, Pneumonia
Pediatrics, Reactive Airway Disease
Pediatrics, Respiratory Distress Syndrome
Pneumonia, Bacterial
Pneumonia, Empyema and Abscess
Pneumonia, Immunocompromised
Pneumonia, Mycoplasma
Pneumonia, Viral
Shock, Septic

Other Problems to be Considered:

Empyema
Lung abscess

WORKUP

Section 5 of 12

Lab Studies:

• Leukocytosis with a left shift may be observed in any bacterial infection; however, its absence, particularly in patients who are elderly, should not cause the clinician to discount the possibility of a bacterial infection.

• Leukopenia (usually defined as a WBC count <5000) may be an ominous clinical sign of impending sepsis.

• Assess ABGs for hypoxia and respiratory acidosis.

• Blood cultures show poor sensitivity in pneumonia. Even in pneumococcal pneumonia, results are often negative. Their yield may be better in patients with more severe cases. The use of blood cultures only rarely dictates a change in antibiotic use.

• Hyponatremia (sodium level <130 mEq/L) and microhematuria may be associated with Legionella pneumonia.

• Sputum examination may be supplemented by using a Legionella-specific fluorescent antibody. However, this technique has a high false-negative rate.

• Urinary antigen testing for Legionella serogroup 1 organisms is accurate. However, as many as 30% of infections are not caused by serogroup 1 organisms.

• Pneumococcal antigen tests for serum, urine, and saliva samples have been developed.

• A Legionella serum antibody titer of 1:128 or more is suggestive of the diagnosis.

• Antigen-antibody testing has little clinical effect in the ED, although it may help in recalcitrant or unclear cases.

• Culture pleural effusions or frank empyema fluid, and perform Gram staining.

• A pulse oximetry finding of <95% indicates significant hypoxia.

• Consider using the patient's Pneumonia Severity Index (PSI) score as a guide for inpatient care and mortality risk. Note that PSI score may underestimate the patient's need for admission (ie, a young otherwise healthy patient who is vomiting or has social factors that precludes him or her taking the medicine). Conversely, the PSI score tends to overestimate the mortality in the higher risk patients. See PSI calculator.

Imaging Studies:

• Chest radiography

• Air bronchograms may be observed in the presence of S pneumoniae. Frank consolidation and air bronchograms have been associated with a higher incidence of bacteremia.

• Cavitary lesions and bulging lung fissures may be observed with Klebsiella pneumoniae infection.

• Cavitation and associated pleural effusions are observed in cases of S aureus infection, anaerobic infections, gram-negative infections, and tuberculosis.

• Legionella has a predilection for the lower lung fields.

• Klebsiella has a tendency to occur in the upper lobes.

• In unclear cases, high-resolution CT scanning of the lungs may aid in the diagnosis.

Other Tests:

• Sputum examination may be performed.

• An adequate specimen must have fewer than 10 oral squamous epithelial cells per low-power field.

• The WBC count should be more than 25 per low-power field.

• A single predominant microbe should be noted at Gram staining, although mixed flora may be observed with anaerobic infections.

• Often, patients cannot produce an adequate specimen. Many specimens produced are so contaminated by oral materials that they are unusable.

• Cultures of the sputum have similar limitations. To be accurate, only specimens that have been examined microscopically and that have satisfied the criteria above should be submitted for culturing.

• Blood cultures have limited value.

• Positive findings correlate well with the causative agent.

• Findings are positive in approximately 40% of cases. (This rate is true even in pneumococcal pneumonia, which has the highest association with positive culture findings.)

• Cultures require 24 hours (minimum) to incubate.

• Findings probably have minimal clinical effect in treating bacterial pneumonia.

• Urine assays are available for the rapid detection of Legionella and pneumococcal antigens. These fast card-type assays have been developed recently, may be performed at the bedside, and may be useful in unclear cases or when the choices for antimicrobial therapy are limited.

• An elevated international normalized ratio has been associated with more severe illness. This finding may herald the development of disseminated intravascular coagulation.

Procedures:

• Bronchoscopy

• Transtracheal aspiration for culturing

• Thoracentesis

TREATMENT

Section 6 of 12

Prehospital Care:

• For patients with mild shortness of breath, only supplemental oxygen may be required for ventilatory support.

• Patients in respiratory failure may require endotracheal intubation and ventilation. An alternative to intubation may be use of a CPAP mask.

• Patients with hypotension and/or tachycardia may benefit from an intravenous crystalloid bolus in the field.

• Many individuals with pneumonia also have volume depletion. In elderly patients with underlying cardiac disease, take care to avoid aggressive fluid administration, which may cause volume overload.

Emergency Department Care:

• Mild dyspnea may resolve with oxygen administered with a nasal cannula.

• Moderate dyspnea requires high oxygen concentrations, such as those provided by a Venti-mask or partial rebreathing face mask. Use these masks with caution in patients with COPD.

• Patients with COPD who need high oxygen concentrations may require intubation.

• Administer ventilatory support when simple supplemental oxygen is not sufficient or when the patient cannot cope with the work of breathing.

• Use of a CPAP mask may be an alternative to intubation in some cases. Patients who are awake and can tolerate mask application may avoid intubation. Nasal CPAP usually is not as well tolerated as a full mask (which covers both the nose and mouth) in the emergent situation.

• Other treatments may include the following:
  • Empiric antimicrobial therapy

• Hydration

• Correction of electrolyte levels

• Chest physiotherapy

Consultations:

• Consultation with infectious disease and/or pulmonary specialists may be of benefit in unclear or difficult cases.

• Critical care specialists may aid in the treatment of admitted patients who require a CPAP mask or intubation.

• Pharmacy and/or infection control may provide information about typical resistance patterns observed in hospitalized patients.

MEDICATION

Section 7 of 12

The mainstay of drug therapy for bacterial pneumonia is antibiotic treatment. The choice of agent is based on the severity of the patient's illness, host factors (eg, comorbidity, age), and the presumed causative agent. Although intravenous penicillin G is currently not favored, doses in the range of 20-24 million U/d result in serum levels that exceed minimum inhibitory concentration levels of most resistant pneumococci. Second-generation cephalosporins maintain the gram-positive activity of first-generation cephalosporins, and they add activity against Proteus mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Third-generation cephalosporins have wider activity against most gram-negative bacteria (eg, Enterobacter, Citrobacter, Serratia, Neisseria, Providencia, Haemophilus species), including beta-lactamase–producing strains.

The role of glucocorticoids in acute bacterial pneumonia is not yet clear. Classic teaching warns that the use of glucocorticoids in infection may impair the immune response. However, findings show that local pulmonary inflammation may be reduced with systemic glucocorticoids. In the future, these drugs may be a useful adjunct in the immunocompetent patient.

Outpatients are given oral agents, and, for the most part, parenteral medications are given to admitted patients. This rationale does not preclude the clinician from giving an initial intravenous dose of antibiotics in the ED and then sending the patient home on oral agents, if the patient's condition warrants such action. The patient's condition, infection severity, and microorganism susceptibility should determine the proper dose and route of administration.

A rational approach may be to administer an oral extended-spectrum macrolide or amoxicillin and clavulanate (Augmentin) to those with mild, outpatient disease. Oral fluoroquinolone may be substituted if a comorbidity or allergy to the first-line agents is present or for good dosing compliance. Admitted patients should receive intravenous therapy, a third-generation cephalosporin alone or with a macrolide. An alternative regimen would be intravenous fluoroquinolones.

Drug Category: Antibiotics -- The best initial antibiotic choice is thought to be a macrolide. Macrolides provide the best coverage for the most likely organisms in community-acquired bacterial pneumonia. Macrolides have effective coverage for gram-positive, Legionella, and Mycoplasma organisms. Azithromycin administered intravenously may be an alternative to intravenous erythromycin.

Macrolides, as a class, have the potential disadvantage of causing GI upset. Compared with erythromycin, newer agents have fewer GI adverse effects and drug interactions, although all macrolides have the potential for drug interactions similar to those of erythromycin. Newer macrolides offer improved compliance because of reduced dosing frequency, improved action against H influenzae, and coverage of Mycoplasma species (unlike cephalosporins). The main disadvantage is cost.

Macrolides are primarily recommended for the treatment of community-acquired pneumonia in patients younger than 60 years who are nonsmokers without comorbidity. Give special consideration to recommendations for antibiotic use in patients with comorbidity or those with community-acquired pneumonia who are older than 60 years. While patients in this group are still susceptible to S pneumoniae, they should receive treatment for broader coverage that includes Haemophilus, Moraxella, and other gram-negative organisms. Therefore, a prudent course of action for empiric outpatient therapy is to include (1) one of the macrolide agents described previously plus a second- or third-generation cephalosporin or amoxicillin and clavulanate or (2) trimethoprim and sulfamethoxazole as a single agent.

Second-generation cephalosporins also provide good coverage against Haemophilus and Moraxella species and provide adequate activity against gram-positive organisms. Of these agents, cefprozil, cefpodoxime, and cefuroxime seem to have better in vitro activity against S pneumoniae. Second-generation cephalosporins are not effective against Legionella or Mycoplasma species. These drugs generally are well tolerated, but cost may be a factor. Oral second-generation and third-generation cephalosporins offer increased activity against gram-negative agents and may be effective against ampicillin-resistant S pneumoniae.

The combination of trimethoprim and sulfamethoxazole may be used in the patient with pneumonia and a history of COPD or smoking. It may be used as a single agent in younger patients in whom a Haemophilus species is the suspected agent. It is well tolerated and inexpensive. Allergic reactions more often are associated with drugs in this class than with other antibiotics. Reactions span the spectrum from simple rash (most likely) to Steven-Johnson syndrome and toxic epidermal necrolysis (rare). Many potential drug interactions exist.

Patients who have moderate clinical impairment or comorbidity are best treated with parenteral agents and, unless a particular agent is strongly suspected, broad coverage should be afforded. Regimens for this use include a macrolide plus a second- or third-generation cephalosporin, (as single agents) amoxicillin and sulbactam (Unasyn), piperacillin and tazobactam (Zosyn), or ticarcillin and clavulanate (Timentin). These last 3 are not described in detail here. Please consult the Sanford Guide for more information.

Intravenous cephalosporins may be combined with a macrolide agent. They broaden the gram-negative coverage, and in the case of third-generation agents, they may be effective against resistant S pneumoniae. Also, some third-generation agents are effective against Pseudomonas, whereas second-generation agents are not.

When a severely ill patient has features of sepsis and/or respiratory failure, and/or when neutropenia is known or suspected, treatment with an intravenous macrolide is combined with an intravenous third-generation cephalosporin and vancomycin. An alternative regimen may include imipenem, meropenem, or piperacillin and tazobactam plus a macrolide and vancomycin. A fulminant course also must raise the suspicion of infection with Legionella or Mycoplasma species, Hantavirus, psittacosis, or Q fever.

Fluoroquinolones, including levofloxacin, moxifloxacin, and gatifloxacin, may also be used. They are available in oral and parenteral forms and have convenient dosing regimens, which allow easier conversion to oral therapy that results in good patient compliance.

All agents discussed above are for use in persons older than 5 years. In children younger than 5 years, initial treatment of pneumonia includes intravenous ampicillin or nafcillin plus gentamicin or cefotaxime (for neonates), and ceftriaxone or cefotaxime can be administered as a single agent (for >28 d to 5 y). An alternative regimen includes a penicillinase-resistant penicillin plus an antipseudomonal aminoglycoside.

Outpatient treatment of mild-to-moderate pneumonias in children usually involves agents similar to those used for acute otitis media. Most of the pneumonias in these patients probably have a viral cause. In children who have features suggesting a bacterial etiology (eg, an infiltrate on chest radiograph and/or positive findings at sputum Gram staining), the administration of antibiotics may be good clinical practice. In these cases, many clinicians begin empiric therapy with amoxicillin, but its spectrum of activity is lacking because children in this group who do not have nonviral pneumonia usually have an infection caused by S pneumoniae and Mycoplasma species. H influenzae type B has been less common since the introduction of the HIB vaccine. Children younger than 2 years may still be at risk for H influenzae type B infection because their immune response is not sufficient, as it is in older children. A typical regimen for outpatient therapy may include a new macrolide agent or a second- or third-generation cephalosporin. Cost is a potential drawback for all agents.

Drug Name	Azithromycin (Zithromax) -- In otherwise uncomplicated pneumonia, initial DOC; covers most potential etiologic agents, including Mycoplasma species. Compared with other drugs, causes less GI upset; potential for good compliance because of reduced dosing frequency. Has better action against H influenzae compared with erythromycin. Main disadvantage is cost.
Adult Dose	Day 1: 500 mg PO Days 2-5: 250 mg PO qd Alternative: 500 mg IV qd
Pediatric Dose	Day 1: 10 mg/kg PO Days 2-5: 5 mg/kg PO qd
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	IV-site reactions can occur; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Drug Name	Clarithromycin (Biaxin) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. Another initial DOC in otherwise uncomplicated pneumonia. Appears to cause more GI symptoms (eg, gastric upset, metallic taste) than azithromycin.
Adult Dose	500 mg PO bid for 10 d
Pediatric Dose	<6 months: Not recommended >6 months: 7.5 mg/kg PO bid for 10 d; not to exceed 500 mg/dose
Contraindications	Documented hypersensitivity; coadministration of pimozide
Interactions	Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, HMG CoA–reductase inhibitors; levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Drug Name	Erythromycin (EES, Erythrocin, Ery-Tab) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. Covers most potential etiologic agents, including Mycoplasma species. Regimen PO may be insufficient to adequately treat Legionella species. Less active against H influenzae. Although standard course of treatment is 10 d, treatment until patient is afebrile for 3-5 d is a more rational approach. May result in GI upset, causing some to prescribe an alternative macrolide or change to tid dosing.
Adult Dose	500 mg PO qid or 333 mg PO tid Hospitalized patients with severe pneumonia: 1 g IV q6h Alternative: 15-20 mg/kg/d IV divided q6h
Pediatric Dose	7.5 mg/kg/d PO divided bid Alternative: 20-40 mg/kg/d IV divided q6h or as constant infusion; not to exceed 4 g/d
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Amoxicillin and clavulanate (Augmentin) -- Alternative for patients who are allergic or intolerant to macrolides. Usually well tolerated and provides good coverage to most infectious agents. Not effective against Mycoplasma and Legionella species. Cost is a problem.
Adult Dose	500/125 or 875/125 mg PO bid for 10 d or until afebrile for 3-5 d Augmentin XR (1000/62.5): 2 tab PO bid for 10 d or until afebrile for 3-5 d
Pediatric Dose	25-45 mg/kg/d PO divided q12h >3 months: Base dose on amoxicillin content; because of different amoxicillin–clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg
Contraindications	Documented hypersensitivity
Interactions	Coadministration with warfarin or heparin increases risk of bleeding
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Give for a minimum of 10 d to eliminate organism and prevent sequelae (eg, endocarditis, rheumatic fever); after treatment, order cultures to confirm eradication of streptococci

Drug Name	Doxycycline (Doryx, Bio-Tab) -- Alternative agent for patients who cannot tolerate macrolides or penicillins. Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose	100 mg PO bid for 10 d or until afebrile for 3-5 d
Pediatric Dose	<8 years: Not recommended >8 years: 2-5 mg/kg/d PO qd or divided bid; not to exceed 200 mg/d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider determining drug serums in prolonged therapy; tetracycline use during tooth development (last half of gestation through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Vancomycin (Vancocin) -- Classified as glycopeptide agent with excellent gram-positive coverage, including methicillin-resistant S aureus. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h before next dose. Use CrCl rate to adjust dose in patients with renal impairment.
Adult Dose	500 mg IV q6h or 1 g IV q12h
Pediatric Dose	10 mg/kg IV q6h Neonates: 15 mg/kg IV initially; administer over 1 h
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; with concurrent use, risk of nephrotoxicity may increase above that associated with aminoglycoside use alone; neuromuscular blockade may be enhanced when used concurrently with nondepolarizing muscle relaxants
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal failure, neutropenia; red man syndrome is caused by too-rapid IV infusion (dose given over a few min) but rarely happens when dose given as 2-h administration or PO or IP; red man syndrome is not an allergic reaction

Drug Name	Trimethoprim and sulfamethoxazole (Bactrim) -- Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, inhibiting folic acid synthesis. Results in inhibition of bacterial growth. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens except Pseudomonas aeruginosa. Each double-strength tab (Bactrim DS or Septra DS) contains 160 mg TMP and 800 mg SMZ.
Adult Dose	160 mg TMP/800 mg SMZ PO bid for 10 d
Pediatric Dose	<2 months: Not recommended >2 months: 8 mg TMP/kg/d PO divided bid
Contraindications	Documented hypersensitivity; megaloblastic anemia caused by folate deficiency
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase zidovudine levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Discontinue at first appearance of rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, patients with chronic alcoholism, elderly patients, those receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in G-6-PD deficiency; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Drug Name	Levofloxacin (Levaquin) -- L stereoisomer of the D/L parent compound ofloxacin (D form is inactive). Good monotherapy that gives extended coverage against Pseudomonas species as well as excellent activity against pneumococcus. The 750-mg dose is as well tolerated as the 500-mg dose and is more effective. Agent acts by inhibition of DNA gyrase activity. PO form has bioavailability that reportedly is 99%. Other fluoroquinolones with activity against S pneumoniae may be useful and include moxifloxacin, gatifloxacin, and gemifloxacin.
Adult Dose	750 mg PO/IV qd for 7-14 d
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); do not administer within 24 h of live typhoid vaccine (reduces vaccine effects)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	In prolonged therapy, periodically evaluate organ system (eg, renal, hepatic, hematopoietic) functions; adjust dose in renal function impairment (with hemodialysis, CAPD, or CrCl <20 mL/min, administer 250 mg q48h; with CrCl 20-49 mL/min, administer 250 mg q24h); superinfections may occur with prolonged or repeated antibiotic therapy; caution in breastfeeding Resistance to these compounds emerging

Drug Name	Cefaclor (Ceclor) -- Second-generation cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. Determine proper dosage and route based on condition of patient, severity of infection, and susceptibility of causative organisms.
Adult Dose	500 mg PO tid for 10 d
Pediatric Dose	20-40 mg/kg/d PO q8-12h
Contraindications	Documented hypersensitivity
Interactions	Alcoholic beverages consumed <72 h after administration may produce disulfiramlike reactions; may increase hypoprothrombinemic effects of anticoagulants; coadministration with potent diuretics and aminoglycosides (eg, loop diuretics) may increase nephrotoxicity (monitor renal function closely)
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Administer half dose if CrCl is 10-30 mL/min and quarter dose if <10 mL/min; bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy

Drug Name	Cefprozil (Cefzil) -- Binds to one or more of the penicillin-binding proteins, inhibiting cell wall synthesis and resulting in bactericidal activity.
Adult Dose	500 mg PO qd for 10 d
Pediatric Dose	<12 years: 7.5-15 mg/kg/d PO divided q12h for 10 d >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Probenecid increases effect; coadministration with furosemide and aminoglycosides increases nephrotoxic effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dosage in renal impairment

Drug Name	Cefuroxime (Ceftin, Kefurox, Zinacef) -- Second-generation cephalosporin maintains the activity against gram-positive organisms that first-generation cephalosporins have. Adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Condition of the patient, severity of infection, and susceptibility of microorganism determines proper dose and route of administration.
Adult Dose	250 mg PO bid for 10 d
Pediatric Dose	<6 months: 20-50 mg/kg/d IV q12h Infants and children: 75-150 mg/kg/d IV q8h; not to exceed 6 g/d
Contraindications	Documented hypersensitivity
Interactions	Disulfiramlike reactions may occur when alcohol is consumed within 72 h after administration; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patients receiving potent diuretics such as loop diuretics; coadministration with aminoglycosides increase nephrotoxic potential
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Administer half dose if CrCl is 10-30 mL/min and quarter dose if CrCl <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy

Drug Name	Ceftriaxone (Rocephin) -- Third-generation cephalosporin with broad-spectrum and gram-negative activity, low efficacy against gram-positive organisms, and high efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. Considered DOC for parenteral agents in community-acquired pneumonia.
Adult Dose	0.5 g IV q12h or 2 g IV qd
Pediatric Dose	>7 days to 6 months: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d >6 months: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in breastfeeding and allergy to penicillin

Drug Name	Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime) -- Third-generation cephalosporin with broad-spectrum and gram-negative activity, low efficacy against gram-positive organisms, and high efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Adult Dose	1-2 g IV q8-12h
Pediatric Dose	<6 months: 30 mg/kg IV q12h >6 months to <12 years: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Name	Linezolid (Zyvox) -- Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Used as alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci. Effective against MRSA and penicillin-susceptible S pneumoniae infections.
Adult Dose	400-600 mg PO/IV q12h for 10-28 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May cause hypertension when used concomitantly with adrenergic agents including pseudoepinephrine, sympathomimetic agents, vasopressor or dopaminergic agents (reduce dose of dopamine or epinephrine if concurrent use required); serotonin syndrome may occur if used concomitantly with serotonergic agents including tricyclic antidepressants, meperidine, dextromethorphan, trazodone, venlafaxine, and selective serotonin reuptake inhibitors
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Has mild MAOI properties and has potential to have same interactions as other MAOIs; caution in uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism, and patients who are at increased risk for bleeding, have preexisting thrombocytopenia, receive concomitant medications that may decrease platelet count or function, or who may require > 2 wk of therapy (monitor platelet counts); unnecessary use may lead to development of resistance to drug

FOLLOW-UP

Section 8 of 12

Further Inpatient Care:

• Direct the use of antibiotic agents based on laboratory data as well as clinical response.

• Unresponsive cases may require fiberoptic bronchoscopy or open lung biopsy for definitive diagnosis.

• Administer adequate respiratory support (eg, as simple as low-flow oxygen or as complex as assisted ventilation), as the patient's clinical situation dictates.

• Pulmonary toilet may include active suction of secretions, chest physiotherapy, positioning to promote dependent drainage, and incentive spirometry to enhance elimination of purulent sputum and to avoid atelectasis.

• Systemic support may include proper hydration, nutrition, and mobilization to create a positive host milieu to fight infection and speed recovery. Early mobilization of patients, with encouragement to sit, stand, and walk when tolerated, speeds recovery.

Further Outpatient Care:

• When treated as an outpatient, the patient must undergo adequate follow-up evaluations.

• A follow-up chest radiograph should be obtained in about 6 weeks to ensure clearing of the infiltrate and to assess persistent abnormality of the lung parenchyma (eg, scarring, bronchiectasis).

• In patients in whom a precipitating factor was tumoral obstruction of an airway, the infiltrate may fail to clear, or the tumor may be depicted on a chest radiograph. CT scans may be of benefit in unclear cases.

In/Out Patient Meds:

• Antibiotic therapy is the mainstay of treatment of bacterial pneumonia. However, patients who have bronchospasm with infection benefit from inhaled bronchodilators, administered by means of a nebulizer metered-dose inhalers.

Transfer:

• Transfer, if needed, is safe for a patient in otherwise stable condition who is being admitted for antibiotic therapy and pulmonary toilet.

• Patients who are severely ill and those with signs of respiratory failure, sepsis, and/or neutropenia must be stabilized prior to transfer.

Deterrence/Prevention:

• Cessation of smoking

• Immunization

• Administration of influenza vaccine decreases fall and/or winter risk of viral influenza, which decreases the risk of bacterial superinfection. This vaccine is especially important in patients who are elderly and in those with comorbidity.

• Pneumococcal vaccines are effective but underused. Administer these to asplenic, transplant, and renal patients; administration in patients who are elderly and in those with comorbidity may not be unreasonable.

Complications:

• Local destruction of lung tissue due to infection (may occur, with subsequent scarring)

• Frank cavitation

• Bronchiectasis

• Empyema

• Pulmonary abscess

• Respiratory failure

• Acute respiratory distress syndrome

• Ventilator dependence

• Superinfection

• Death

Prognosis:

• The prognosis generally is good in the otherwise healthy patient with uncomplicated pneumonia.

• These factors, alone or in combination, increase morbidity and mortality: advanced age, aggressive organisms (eg, Klebsiella species, Legionella species, resistant S pneumoniae), comorbidity, respiratory failure, neutropenia, and features of sepsis.

Patient Education:

• Encourage cessation of smoking and heavy use of alcohol.

• Encourage keeping teeth in good repair.

• Instruct patients at risk to receive appropriate influenza immunization.

• Patients, particularly elderly and debilitated patients, with symptoms such as dyspnea or fever and rigors should seek prompt care.

• For excellent patient education resources, visit eMedicine’s Pneumonia Center. Also, see eMedicine’s patient education article Bacterial Pneumonia.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Use caution in patients who are elderly or debilitated. If bacteremia is present in persons with pneumococcus who are older than 80 years, the mortality rate remains approximately 40%, even with treatment.

• Empiric therapy for the hospitalized patient should be initially broad and cover the likely causative organisms.

• Always consider the possibility of Legionella infection because delayed treatment significantly increases mortality.

• Remember that the most prevalent causative organism is pneumococcus regardless of the host; empiric therapy must be selected with this in mind.

• Many regions have guidelines for evaluation and treatment of community-acquired pneumonia. This usually includes a minimum time from door to antibiotic of 4 hours or less. Failure to abide by these time parameters may be associated with poor outcome. When in doubt, administer the first antibiotic dose.

TEST QUESTIONS

Section 10 of 12

CME Question 1: In the patient with pneumonia, which of the following factors requires admission?

A: Inability to take anything by mouth
B: Production of blood-tinged sputum
C: Multilobar involvement on chest radiographs
D: A and C
E: All of the above

The correct answer is D: A patient who cannot take anything by mouth becomes dehydrated quickly and cannot be expected to comply with oral antibiotic therapy. Multilobar involvement implies disease that is worse than that with a single-lobe infiltrate. Blood-tinged sputum is not in itself a problem, but a dark currant-jelly sputum appearance, which is suggestive of infection with Klebsiella organisms, is worrisome.

CME Question 2: Which of the following are acceptable antibiotic regimens for the hospitalized patient with suspected bacterial pneumonia?

A: Intravenous second- or third-generation cephalosporin and a macrolide
B: Intravenous levofloxacin
C: Intravenous fluoroquinolone and clindamycin
D: All of the above
E: None of the above

The correct answer is D: All regimens listed are applicable. Intravenous second- or third-generation cephalosporin and a macrolide are used for community-acquired pneumonia, and intravenous levofloxacin is an alternative. Both provide adequate coverage for the bacterial pathogens usually encountered, as well as for Legionella species. Intravenous fluoroquinolone with clindamycin may be used when an aspiration is suspected.

Pearl Question 1 (T/F): Pneumococci are the most common cause of bacterial pneumonia.

The correct answer is True: Bacterial pneumonia caused by Streptococcus pneumoniae remains the most common cause for all bacterial pneumonias.

Pearl Question 2 (T/F): In all patients with pneumonia, a follow-up chest radiograph should be obtained.

The correct answer is True: Even with clinical resolution, a follow-up chest radiograph obtained 6 weeks after treatment should be obtained to rule out an underlying parenchymal abnormality (eg, tumor) as an etiology of the pneumonia.

Pearl Question 3 (T/F): Blood cultures have a significant role in the management of bacterial pneumonia.

The correct answer is False: Blood cultures have a small role; they have low rates of positive findings (only 40% of findings are positive even with pneumococcal cases), and findings may not become positive for 24-48 hours. Blood cultures are obtained as a traditional part of the workup; but support for their use is waning.

Pearl Question 4 (T/F): Prognosis for patients with Legionella pneumonia is poor with adequate antibiotic therapy.

The correct answer is False: Unfortunately, Legionella often affects patients who are elderly and infirm. Unless treated early and aggressively, the mortality rate approaches 75%.

PICTURES

Section 11 of 12

Caption: Picture 1. Lateral image in a patient with right upper lobe pneumonia. Note the increased anteroposterior chest diameter, which is suggestive of chronic obstructive pulmonary disease (COPD).
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Caption: Picture 2. Lateral image in a patient with bilateral lower lobe pneumonia. Note the spine sign, or loss of progression of radiolucency of the vertebral bodies.
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Caption: Picture 3. Early right middle lobe pneumonia.
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BIBLIOGRAPHY

Section 12 of 12

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